Bactericidal-fungicidal compositions



United States Patent BACTERICIDAL-FUNGICIDAL COMPOSITIONS Jerome F.Fredrick, New York, N.Y., assignor to The Dodge Chemical Company,Boston, Mass., at corporation of Massachusetts No Drawing. ApplicationJuly 29, 1958 Serial No. 751,637

Claims. (Cl. 167-33) 'This invention relates to bactericidal-fungicidalcompositions containing as active ingredients the quaternary ammoniumalkyl derivatives of ehlo'rokojic acid (2-chloromethyl-S-hydroxygammapyrone) and certain related compounds, which are activated in thepresence of metal- 1ic ions in water.

The use of quaternary ammonium compounds for purposes of disinfection iswell known. However, such prior compounds have had the serious defectthat they are inactivated by metallic ions encountered in various watersand biological fluids.

In a brief summary of this invention, ithas now, been found that a groupof new quaternary ammonium compounds prepared by the reaction ofchlorokojic acid and certain derivatives thereof with long alkyltertiary amines derived from cocoanut fatty acids, and particularly thedialkyl derivatives of these amines having a minimum carbon chain ofeight units and a maximum of eighteen units, are not adversely affectedby metallic salts, and indeed are activated by contact with suchinorganic materials so that an increase in their bactericidal andfungicidal properties occurs. These new compounds are defined by thestructure ing between 8 and 18 carbon atoms, preferably an even a numberand with no more than two double bonds; R is a short aliphatichydrocarbon; and X is an inert anion, preferably a halide or sulfate.Fungicidal and bactericidal compositions are prepared by mixing theabove compounds With a carrier, for example fr0m 0.l to 1.0 percent byWeight in Water, with or without other additives, for application asdisinfectants to plants and inanimate objects. a

The new quaternary ammonium compounds can be prepared by refluxingchlorokojic acid, or one of its derivatives, dissolved in the tertiaryamine, extracting the quaternary with warm Water, filtering, andconcentrating the filtrate to an active gel by evaporation. Thisinvention may be better understood by reference to the followingexamples. i

EXAMPLE 1 where R" can be any and all of the following types ofaliphatic hydrocarbons, and, according to this example, in the followingproportions! Carbon chain length: Portion by weight Saturated- C-lO 7C-18 I 2 i i Unsaturatedt C-18 (one double bond) 6 (as oleic) CA8 (twodouble bonds) ,2 (as linoleic) i When the above gel is dissolved inwater to give solutions, for example from 0.1 to 1.0% by weight activematerial, these solutions have biocidal properties with regard tobacteria and fungal spores. The solutions are also surface-active andare of cationic nature.

It has been further found that these disinfecting solutions are notadversely affected by water containing metal salts, but are insteadactivated in so far as the abovementioned biocidal propertiesareconcerned. Furthermore, waters up to and includingSOO p.p.m. of hardnessdo not cause any decreasein this activity.

Test 1 Fungicidal tests were made by the RDA. Agar Cup F Method(U.S.D.A. Cir. 198, December 1931) using the GHQ-1 F a plus derivativesthereof, and more particularly by the structures 0 ll II HO HO I l I I.t ir i R x R )X and R R I R,.IIIIICH CHzN:-R R, xx

spores only of a ten day culture of a mixed mold Mucor (A.T.C.C.7927-1937); of which a 0.1 cc. suspension was used. This mold wastreated with a 1% water solution 3. a of the gel in Example 1. Theappearance of aclear zone Patented Dec. 22, 1959 p garages 3 surroundingthe cup indicated that the invention was fungistatic and recultures fromthis zone indicated that it was fungicidal. 1% solutions of the abovegel containing 1% ferric ion were similarly tested. The results of thesetests are as follows:

MUCOR SPP. A.T.C.C. 7927-7937 Width of Agent Clear Zone, Reculture mm.

Alone 10 Negative. Plus Fe (1%) 20 Do.

It should be noted that metallic ions such as iron activate both thefungistatic and fungicidal properties of the active compounds.

Test II Bactericidal tests were made using the Phenol Coefficient Method(F.D.A., December 1931) with Salmonella ty'phosa (E. typhosa) Hopkins of24 hour cultures with the following results:

' EfM/phoaa HOPKINS Phenol Coefll- Agent cient of 1% Solution Alrme 250Plus Fe (1%) 35. 6

Again it should be observed that the phenol coeflicient actuallyincreases in the presence of contaminating metal According to currentstudies, the increase in biocidal activity in the presence ofcontaminating metal ions probably occurs through the formation of achelate with divalent metals containing two molesof a quaternary permolecule, and with trivalent metals; containing three moles permolecule, according to the following proposed structure:

EXAMPLE 2 Chlorokojic acid was dissolved in stearyl dimethyl tertiaryamine '(DM18D of the Armour Company), refluxed, and the resultingquaternary ammonium compound separated as in Example 1.

This active compound has the following structure:

CHr N C H311 Hfo1 EXAMPLE 3 Chlorokojic acid, was dissolved in cetyldimethyl ter; tiary amine (DM16D of the'Armour' Company), refluxed andseparated to give the following active quaternary ammonium compound:

w ire E1601 4 EXAMPLE 4 The 6-hydroxymethyl gamma pyrone analogous tochlorokojic acid is dissolved in dimethyl tertiary amine,

refluxed and separated to give biocidally active compounds as follows:

EXAMPLE 5 The following compounds have been similarly prepared and foundto be active:

HO, CIJH: R-fiI-CH Cl CH:

EXAMPLE 6 Kojic acid is converted to the analogous gamma pyridone,refluxed with the dimethyl tertiary amines to give the following activecompounds:

no H

2,2"dichloromethyl 6.6'-dikojyl methane was prepared from kojic acid andconverted to active quaternary compounds as follows;

-omon A o 0 l| ll OH HO soon noon:- cn onion 0 o --0E H0 l MUCH).

on CH;CI A a 0 ,7

I n II OH H0 is I I l I R-N-CH -CH CH NR of on, 011;01

Each of the quaternary ammonium compounds shown in Examples 2 through 8have been tested according to procedures similar to those shown inExample 1 and found to have similar fungicidal and bactericidalproperties. In each of these examples the useful tertiary amines are thesame as those shown in Example 1, that is, a tertiary amine having analiphatic hydrocarbon (R) with between 8 and 18 carbon atoms andpreferably an even number of carbon atoms with not more than two doublebonds. While the biocidally active quaternary compounds can be preparedfrom pure amines as shown in Examples 2 and 3 above, it is well-knownthat mixtures of tertiary amines yielding a mixture of quaternarycompounds such as shown in Example 1 yield a more active material.Dirnethyl tertiary amines have been shown in the examples as thecheapest and most readily available material. However other tertiaryamines such as for example the homologs methyl-ethyl or diethyl, etc.can be employed. Similarly, while the chlorine derivative of kojic acidis shown as the most convenient starting material, the other halides canbe used. While it is preferred that. the anion presentwith thequaternary ammonium compound be'a halide or sulfate, any inert anioncan. be employed. For example, in all of the foregoing steps wherein thechlorine derivative of the kojic acid type molecule was formed withthionyl chloride (S0012), the bromine derivative (and hence the brominequaternary salt) can be formed by substituting for the thionyl chloridea mixture of bromine in glacial acetic acid. These bromine derivativesare much more reactive with the amines than the corresponding chlorinematerials and form the quaternary salt in a much shorter time and at alower temperature.

The metal ions which form biocidally active complexes with thequaternary compounds of this invention include the alkali metals,calcium, magnesium, iron (ferric and ferrous), cobalt (cobaltic andcobaltous), manganese (manaanous) and co per. These complexes are watersoluble and can readily be prepared by adding soluble salts of-thesemetals to water solutions of the quaternaries, followed by drying ifdesired.

It should be noted that all of the quaternary ammonium compounds shownherein have a similar ring structure capable of forming chelates orcomplexes with metal ions and consequently are not deactivated in thepresence of such ions. These active quaternary ammonium compounds can beused as fungus and bacteria disinfectants by mixing with carriers suchas water, dry inert powders, creams, and the like for application toplants and inanimate objects. These compounds have been found to makevery desirable materials for embalming purposes.

It should be understood that this disclosure is for the purpose ofillustration only and that the invention includes all modificationsfalling within the scope of the appended claims.

I claim:

1. A cationic quaternary ammonium compound selected from the groupconsisting of O 0 II II HO- HO I I II t CHPIIIIR N rCHI-IfqR R X H R XRI CHaI%T -R R x where R is a non-acetylenic aliphatic hydrocarbonhaving between 8 and 18 carbon atoms inclusive and not more than twocarbon to carbon double bonds, R is a lower alkyl group and X is aninert anion.

4. A cationic quaternary ammonium compound having the structure BIO--0111-1 14: N H R x where R is a non-acetylenic aliphatic hydrocarbonhaving between 8 and 18 carbon atoms inclusive and not more than twocarbon to carbon double bonds, R is a lower alkyl group and X is aninert anion.

5. A cationic quaternary ammonium compound having the structure HO R R II I x a x where R is a non-acetylenic aliphatic hydrocarbon havingbetween 8 and 18 carbon atoms inclusive and not more than two carbon tocarbon double bonds, R is a lower alkyl group and X is an inert anion.

6.. A cationic quaternary ammonium compound having the structure where Ris a non-acetylenic aliphatic hydrocarbon having between 8 and 18carbons atoms inclusive and not more than two carbon to carbon doublebonds, R is a lower alkyl group and X is an inert anion.

7. A cationic quaternary ammonium compound having the structure 8. Acationic quaternary ammonium compound having the. structure where R is anon-acetylenic aliphatic hydrocarbon having. between 8 and 18 carbonatoms inclusive and not more than two carbon to carbon double bonds, Ris a. lower alkyl group and X is an inert anion.

9. A cationic quaternary ammonium compound having the structure where Ris a non-acetylenic aliphatic hydrocarbon having between 8 and 18 carbonatoms inclusive and not more than two carbon to carbon double bonds, Ris a lower alkyl group and X is an inert anion.

10. A cationic quaternary ammonium compound hav ing the structure whereR is a non-acetylenic aliphatic hydrocarbon having between 8 and 18carbon atoms inclusive and not more than two carbon to carbon doublebonds, R isa lower alkyl group and X is an inert anion.

References Cited in the file of this patent Wolf etal.: Chem. Abstracts,vol. 45, col. 1.0298. (1951).

Fitzgerald et a1.: Chem. Abstracts, vol. 47, col. 10055-6,

Woods: I. Am. Chem. Soc., vol. 77, pp. 1702 (1955.).

1. A CATIONIC QUATERNARY AMMONIUM COMPOUND SELECTED FROM THE GROUPCONSISTING OF